The re-evaluation of sweeteners by the European Food Safety Authority

(EFSA)

Federica Lodi

Food Ingredients and Packaging Unit (FIP), Food Additives Team

Research in Food Safety

Luxembourg

26 November2019

Food additives re-evaluation

Re-evaluation of sweeteners

Protocol on hazard identification and characterisation

Working Group Sweeteners

Outline of presentation

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Re-evaluation vs New Application

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Food additives already

permittedbefore

Food additives authorised after

Re-evaluation

New applications

20 Jan 2009

Re-evaluation vs New Application

420 Jan 2009

Applicant

European Commission

EFSA

• Scientific information

Dossier

European Commission

EFSA

9 months (+ stop-the-clock) from

receipt of a valid application

• Published literature

• Previous evaluations

• Unpublished reports

All available data

Manufacturers

Other scientificbodies

Food business operators

Researchers

Calls for data: Technical, exposure, biological/toxicological

Single mandate

Scientific Assessment

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Technical part

• Identity of the substance

•Specifications

•Analytical results

•Manufacturing process

•Methods of analysis in food

•Stability and fate in food

Questions

•What is the food additive?

•Are we talking about the same substance that it was assessed at the time of the initial authorisation?

•What are residuals/by products resulting from manufacturing process/storage/interaction with food?

HAZARD IDENTIFICATION

Scientific Assessment

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Biological and toxicological

data

•ADME (absorption, metabolism, distribution, excretion)

•Genotoxicity (in vitro, in vivo)

•General toxicity (short-term, sub-chronic, chronic, carcinogenicity)

•Reproductive toxicity

• Immunotoxicity

•Other studies

Questions

•What happen to the additive once it is ingested with the diet? Is it absorbed? To what is it metabolised?

•Are adverse effects identified from the available studies?

• If yes: can a dose response be identified?

• If no: true lack of effect or lack of data?

•Are the data available still reliable compared to today’s standards?

HAZARD CHARACTERISATION

Sweeteners to be re-evaluated under Regulation (EC) No 257/2010

Re-evaluation of sweeteners: list of substances

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E Number Food additive(s) Substance

E 420 Sorbitols E 420 (i)E 420(ii)

SorbitolSorbitol syrup

E 421 Mannitols E 421(i)E 421(ii)

Mannitol by hydrogenationMannitol manufactured by fermentation

E 950 Acesulfame K

E 951(a) Aspartame(a)

E 952 Cyclamates E 952(i)E 952(ii)E 952(iii)

Cyclamic acidSodium cyclamateCalcium cyclamate

E 953 Isomalt

E 954 Saccharin and its Na, K and Ca salts E 954(i)E 954(ii)E 954(iii)E 954(iv)

SaccharinSodium saccharinCalcium saccharinPotassium saccharin

E 955 Sucralose

E 957 Thaumatin

E 959 Neohesperidine dihydrochalcone

E 961 Neotame

E 962 Salt of aspartame-acesulfame

E 965 Maltitols E 965(i)E 965(ii)

MaltitolMaltitol syrup

E 966 Lactitol

E 967 Xylitol

E 968 Erythritol

(a) Aspartame: re-evaluation already completed by EFSA in 2013

Deadline:

by end December 2020

Technical/Biological and toxicological data: closed in June 2018

- Procurement contract (ended June 2019): inventory and synthesis

Occurrence data: Call for food additives usage level and/or concentration data in food and beverages intended for human consumption (Batch 7) closed in October 2018

2nd call for Technical data: information on particle size and particle size distribution launched on 13 May 2019- deadline 13 September 2019

Re-evaluation of sweeteners: calls for data

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New procurement contract: started on 28 October 2019

to perform extensive literature searches in order to identify and retrieve all

related information on both technical and biological/toxicological data on the 15

sweeteners, published after the last evaluation of the SCF or EFSA.

Re-evaluation sweeteners: new literature searches

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Background information:As outlined in Regulation (EC) No 257/2010 on the re-evaluation of food additives, in the course of the re-evaluation procedure “EFSA shall:

a) examine the original opinion and the working documents of the Scientific Committee on Food (‘SCF’) or EFSA;

b) examine, where available, the original dossier;

c) examine the data submitted by the interested business operator(s) and/or any other interested party;

d) examine any data made available by the Commission and Member States;

e) identify any relevant literature published since the last evaluation of each food additive”.

Two protocols have been developed: One framing the scope of the assessment from the general mandate from

EC (for all steps of RA, except exposure)

One focussing on exposure assessment

Re-evaluation of sweeteners: protocols for RA

Aim:

To define as much as possible beforehand the strategy applied for collecting and

selecting data, appraising the relevant evidence, and analysing and integrating the

evidence in order to draw conclusions that will form the basis for the scientific

opinions.

Iterative/ Planning phase

Impartiality & methodological rigour along the process

Protocols for risk assessment

General European population: the following age groups will be considered a priori:

- Infant below 16 weeks of age, only for Mannitol (E 421), which is the only sweetener permitted in foods for infants and young children, as a carrier for vitamin B12

- Infants ≥ 4 to < 12 months

- Toddlers (young children) ≥ 1 to < 3 years

- Other children ≥ 3 to < 10 years

- Adolescents ≥ 10 to < 18 years

- Adults ≥ 18 to < 65 years

- Elderly adults ≥ 65 years

Sub-populations with anticipated high levels of intake (i.e. diabetics) and sub-population with distinct vulnerabilities to the intake of sweeteners (e.g. individualswith inborn errors of phenylalanine metabolism) will be considered during theassessment.

Re-evaluation of sweeteners: target population

Sub-questions to be addressed in the hazard identification and characterisation of sweeteners

Protocol for assessment of hazard identification and characterisation of sweeteners

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1 (a-d), 2 and 4 (ADME, genotoxicity, MoA): narrative approach3 (a, b) (animal and human studies): systematic review

Number Sub-question

1a What is the ADME of sweeteners in humans?

1b What is the ADME of sweeteners in mammalian animal species?

1c How do the human and animal ADME data correlate?

1d Are there any biomonitoring data that contribute to the assessment of ADME?

2 Do any of the substances included in the assessment show a genotoxic potential?

3a Is there a dose-response relationship between the dietary exposure to sweeteners and adverseeffects in humans (observational and interventional studies)?

3b Is there a dose-response relationship between exposure to sweeteners and adverse effects intoxicological studies conducted in experimental animals?

4 Which could be the potential mode(s) of action for the relationships found, if any, betweensweeteners intake and the adverse health outcomes?

Protocol for assessment of hazard identification and characterisation of sweeteners

•Is there a dose-response relationship between the dietary exposure to sweeteners and adverse effects in humans/experimental animals?

Problem formulation

•Open-ended searches; from last SCF/EFSA opinion

• Refinment if neededExtensive Literature Searches

•Two steps: Ti/Ab_full text

•Setting of inclusion/exclusion criteriaScreening the studies for

relevance

•Adapted from the OHAT rating tool (NTP, 2015); 3 tiers

•Modified from the EFSA BPA protocol, 2017

Evaluation of the Risk of Bias/Data extraction

•Modified version of the OHAT (NTP, 2015) and EFSA Guidance on WoE (2017)

•Grouping animal/human studies on the same endpoint

Weighing the body of evidence

•EFSA Guidance on WoE, 2017

•EFSA Guidance on Uncertainties, 2018 Synthesis of the evidence

and uncertainties

Steps and timeline: protocol for assessment of hazard identification and characterisation of sweeteners

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2019 March

•First presentation at Open FAF Panel

2019 April-June

•finalisation of draft protocol

Ongoing: 5 July-19 September 2019

•Public consultation

15 Nov 2019:

•Adoption protocol

End 2019-2020

•Implementation

Steps and timeline: protocol on exposureassessment

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July 2019Protocol endorsed by the Sweetener WG

September 2019Protocol endorsed for public consultation by the FAF Panel

January 2020Protocol adopted by the FAF Panel

2020Assessment of exposure based on the protocol

October 2018Brainstorming started

Re-evaluation of sweeteners

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Engagement and transparency along

the process

Open FAF Plenary (26-28 March, 2019)

Public consultations (2nd part 2019)

Stakeholder event: food additive re-evaluation with focus on sweeteners, Paris, 3 December 2019:

https://www.efsa.europa.eu/en/events/event/technical-stakeholder-event-re-evaluation-authorised-food-additives

PRINCIPLESfor the scientific assessment process

Plan ahead: protocol development

Systematic review process

Impartiality and Methodological rigour along the process

Current organisation of Working Group on sweeteners:

Sub-group for overall strategy for the assessment

Sub-group for technical part

Sub-group for exposure assessment

Interaction between the three subgroups

Re-evaluation of sweeteners: current way of working

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Working Group Sweeteners enlargement

Will evolve in a fully multidisciplinary WG with all areas of expertise: • Chemistry

• Exposure,

• Subchronic/chronic toxicity, genotoxicity, reproductive/developmental toxicity, general toxicology, epidemiology, etc….

Engage with Art.36 organizations (but not only): attract experts to be part of this WG, according to their expertise

Implementation of protocol: future way of working

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